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C家族趋化因子XCL1增强CVB3基因疫苗的抗病毒免疫应答及保护作用

Co-injection with XCL1 plasmid enhanced the protective immune response against CVB3 conferred by DNA vaccines

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【作者】 岳艳徐薇蒋正刚胡林昆李康熊思东

【Author】 YUE Yan,XU Wei#,JIANG Zheng-gang,HU Lin-kun,LI Kang,XIONG Si-dong(Department of Immunology,Shanghai Medical College and Institute for Immunobiology of Fudan University,Shanghai 200032,China)

【机构】 复旦大学免疫生物研究所 复旦大学上海医学院免疫学系复旦大学免疫生物研究所复旦大学上海医学院免疫学系上海200032

【摘要】 为提高以往构建的基因疫苗pcDNA3.1-VP1的抗B3型柯萨奇病毒(CVB3)感染的免疫效果,以编码C家族趋化因子XCL1的质粒pcDNA3.1-XCL1共注射,观察诱导的CVB3特异性免疫应答及CVB3病毒性心肌炎预防效果。将两种质粒各50μg混合后分别于0、2、4、6周肌注免疫小鼠4次,末次免疫后4周分别以5×LD50剂量CVB3攻击小鼠观察保护率,或以3×LD50剂量CVB3感染小鼠观察病毒性心肌炎的诱生。结果显示,与单纯pcDNA3.1-VP1质粒相比,XCL1质粒共注射可增强血清CVB3特异性IgG以及特异性CTL应答。5×LD50病毒攻击后,共注射组体重降低7.28%,而pcDNA3.1-VP1组体重降低10.97%;共注射组28 d保护率达40%,高于pcDNA3.1-VP1组的30%。3×LD50病毒感染后心肌组织病理显示,共注射组心外膜下仅有轻微炎症,心肌内未见炎症细胞浸润,而pcDNA3.1-VP1组除心外膜下有较多淋巴细胞聚集外,心肌内有少量炎症浸润和坏死灶。提示XCL1质粒共注射可增强CVB3特异性体液和细胞免疫应答及抗病毒保护,可有效预防病毒性心肌炎的发生。

【Abstract】 To enhance the effect of our previous constructed pcDNA3.1-VP1 DNA vaccine against Coxsackievirus B3(CVB3),another plasmid encoding XCL1,a C family chemokine,was intramuscularly co-injected.BALB/c mice were co-injected with 50 μg of pcDNA3.1-VP1 and pcDNA3.1-XCL1 4 times at 2 weeks intervals.Four weeks after the last immunization mice were challenged with 5×LD50 of CVB3 to see the the effect of ani-CVB3 protection or mice were infected with 3×LD50 of CVB3 to see the prevention of CVB3-myocarditis.The results showed that increased level of serum IgG and specific CTL response was induced after co-injection with pcDNA3.1-VP1 and pcDNA3.1-XCL1 compared to that induced by pcDNA3.1-VP1 alone.Mice receiving co-injection lost 7.28% of their weights after CVB3 challenge and resulted in 40% of protection,while mice injected with pcDNA3.1-VP1 alone lost 10.97% of their body weights and the protection percentage was 30%.Histopathological analysis showed that fewer inflammatory cells under the epicardium were observed in the hearts of co-immunized mice compared to that of control groups.In conclusion,co-injection with XCL1 plasmid could enhance CVB3 specific systemic immune responses and more efficiently prevent the occurrence of CVB3-induced myocarditis.

【关键词】 CVB3基因疫苗XCL1共注射病毒性心肌炎
【Key words】 CVB3DNA vaccineXCL1co-injectionmyocarditis
【基金】 国家自然科学基金资助项目(30400396);上海市科委产学研究项目(04D211601);上海市医学领军人才资助项目(LJ06011)
  • 【文献出处】 现代免疫学 ,Current Immunology , 编辑部邮箱 ,2008年02期
  • 【分类号】R392
  • 【被引频次】17
  • 【下载频次】187
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